Retinoid-lipid drug carrier

Patent metadata

Field	Value
Publication number	US-2017081663-A1
Application number	US-201615284494-A
Country	US
Kind code	A1
Filing date	Oct 3, 2016
Priority date	Jun 8, 2011
Publication date	Mar 23, 2017
Grant date	—

Abstract

What is described is a pharmaceutical composition for treating a fibrotic disease comprising a drug carrier, which comprises a lipid and a retinoid, and a double-stranded nucleic acid molecule, which comprises an antisense sequence to mRNA encoding human hsp47.

First claim

What is claimed:

1 . A pharmaceutical composition comprising a drug carrier and a double-stranded nucleic acid molecule, wherein the drug carrier comprises a lipid and a compound for facilitating drug delivery to a target cell, consisting of the structure (retinoid) m -linker-(retinoid) n , wherein m and n are independently 0, 1, 2, or 3, except that m and n are not both zero; and wherein the double-stranded nucleic acid molecule comprises the structure (A2) set forth below:
5′ N1-(N)x-Z 3′ (antisense strand)
3′ Z′—N2-(N′)y-z″ 5′ (sense strand)  (A2)
wherein each of N2, N and N′ is an unmodified or modified ribonucleotide, or an unconventional moiety; wherein each of (N)x and (N′)y is an oligonucleotide in which each consecutive N or N′ is joined to the adjacent N or N′ by a covalent bond; wherein each of x and y is independently an integer between 17 and 39; wherein the sequence of (N′)y has complementarity to the sequence of (N)x and (N)x has complementarity to a consecutive sequence in a target RNA; wherein N1 is covalently bound to (N)x and is mismatched to the target RNA or is a complementary DNA moiety to the target RNA; wherein N1 is a moiety selected from the group consisting of natural or modified uridine, deoxyribouridine, ribothymidine, deoxyribothymidine, adenosine or deoxyadenosine; wherein z″ may be present or absent, but if present is a capping moiety covalently attached at the 5′-terminus of N2-(N′)y; wherein each of Z and Z′ is independently present or absent, but if present is independently 1-5 consecutive nucleotides, consecutive non-nucleotide moieties or a combination thereof covalently attached at the 3′-terminus of the strand in which it is present; and wherein (N)x comprises an antisense sequence to the mRNA coding sequence for human hsp47 exemplified by SEQ ID NO:1.

2 . A pharmaceutical composition comprising a drug carrier and a double-stranded nucleic acid molecule, wherein the drug carrier comprises a lipid and a compound for facilitating drug delivery to a target cell, wherein the lipid comprises a compound of formula I

wherein R 1 and R 2 is independently selected from a group consisting of C 10 to C 18 alkyl, C 12 to C 18 alkenyl, and oleyl group; wherein R 3 and R 4 are independently selected from a group consisting of C 1 to C 6 alkyl, and C 2 to C 6 alkanol; wherein X is selected from a group consisting of —CH 2 —, —S—, and —O— or absent; wherein Y is selected from —(CH 2 ) n , —S(CH 2 ) n , —O(CH 2 ) n —, thiophene, —SO 2 (CH 2 ) n —, and ester, wherein n=1-4; wherein a=1-4; wherein b=1-4; wherein c=1-4; and wherein Z is a counterion; and
wherein the double-stranded nucleic acid molecule comprises the structure (A2) as defined in claim 1 .

Assignees

• Nitto Denko Corp

Inventors

• Niitsu Yoshiro
• Knopov Victor
• Payne Joseph E
• Witte Richard P
• Ahmadian Mohammad
• Perelman Loren A
• Akopian Violetta
• Tanaka Yasunobu
• Feinstein Elena
• Avkin-Nahum Sharon
• Kalinski Hagar
• Mett Igor
• Minomi Kenjiro
• Ying Wenbin
• Liu Yun
• Hou Zheng
• Gaudette John A
• Karmali Priya
• Nagarajan Sridhar C

Classifications

• C12N2310/11

  Antisense · CPC title

• A61K47/24

  containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids · CPC title

• A61K47/18

  Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids · CPC title

• A61K47/186

  Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · CPC title